Key Learnings from Clinical Research and Real-World Evidence on Asfotase Alfa Effectiveness in Hypophosphatasia: 10 Years Post-Approval.
Document Type
Article
Publication Date
9-2025
Identifier
DOI: 10.1007/s12325-025-03309-1
Abstract
First reported in 1948, hypophosphatasia (HPP) is a rare systemic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (ALP) enzyme. Patients with HPP experience skeletal and dental manifestations such as rickets/osteomalacia, fractures, pseudofractures, and premature tooth loss, as well as nonskeletal symptoms such as pain and muscle weakness, which result in impaired mobility and poor quality of life. For decades, no specific treatment was available for HPP and the disease was often fatal in infants. Asfotase alfa is a tissue-nonspecific ALP enzyme replacement therapy (ERT) that received first regulatory approval in 2015 in Japan, the European Union, and the United States for the treatment of HPP. This review draws from clinical trial findings, real-world evidence, and relevant case study data demonstrating the safety and effectiveness of asfotase alfa in improving a broad range of skeletal and nonskeletal manifestations in both pediatric and adult patients. Asfotase alfa has been shown to be well tolerated, with manageable side effects. Further, asfotase alfa treatment has improved survival and respiratory outcomes, skeletal outcomes, physical and motor function, pain, disability, and quality of life in patients with HPP. This evidence-based review aims to generate a foundation for improving the understanding of disease pathophysiology, hence enhancing the effectiveness of ERT in patients with HPP.
Journal Title
Advances in therapy
Volume
42
Issue
9
First Page
4270
Last Page
4299
MeSH Keywords
Humans; Hypophosphatasia; Enzyme Replacement Therapy; Recombinant Fusion Proteins; Alkaline Phosphatase; Quality of Life; Child; Treatment Outcome; Adult; Immunoglobulin G
PubMed ID
40715944
Keywords
Asfotase alfa; Bone; Effectiveness; Hypophosphatasia; Quality of life; Treatment.
Recommended Citation
Khan AA, Rush ET, Wakeford C, Staub D, Brandi ML. Key Learnings from Clinical Research and Real-World Evidence on Asfotase Alfa Effectiveness in Hypophosphatasia: 10 Years Post-Approval. Adv Ther. 2025;42(9):4270-4299. doi:10.1007/s12325-025-03309-1
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